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Biomedical subjects

D J Gawkrodger

Publications and source records attributed to D J Gawkrodger.

At least 55 records · Page 3Linked to original sources
PubMed1999

Analysis of a microsatellite polymorphism of the cytotoxic T-lymphocyte antigen-4 gene in patients with vitiligo.

The CTLA-4 gene encodes a T-cell receptor that is involved in the regulation of T-cell activation. Recent studies have demonstrated an association of a microsatellite polymorphism [variant lengths of a dinucleotide (AT)n repeat] lying in exon 3 of the CTLA-4 gene, specifically a 106-bp allele, with autoimmune disorders, such as Graves' disease, autoimmune Addison's disease and autoimmune hypothyroidism. The aim of the present study was to determine whether the same polymorphism of the CTLA-4 gene was associated with vitiligo, a disorder that may have an autoimmune origin and can be present in patients who have one or more autoimmune diseases. CTLA-4 gene microsatellite polymorphisms were determined for 74 vitiligo patients (53 without any autoimmune disorder; 21 with one or more autoimmune disease) and 173 healthy controls, who had no clinical evidence of either vitiligo or any other autoimmune disorder, by polymerase chain reaction amplification of genomic DNA and resolution of the products on polyacrylamide sequencing gels. The frequency of the 106-bp allele was significantly increased (chi2 = 5. 2; P = 0.02) in vitiligo patients as a whole, in comparison with control subjects. However, when the patients were classified according to the absence or presence of an autoimmune disorder, the frequency of the 106-bp allele was significantly increased (chi2 = 14.8; P = 0.0001) only in the group of vitiligo patients who also had an autoimmune disease. However, the fact that 17 of 21 patients also had either autoimmune thyroiditis or autoimmune Addison's disease probably accounts for the apparent association of vitiligo and the 106-bp allele in this patient group. However, it was found that the relative risk of 3.2, conferred by the 106-bp allele in this group of vitiligo patients, was greater than that found for patients with only either Graves' disease, autoimmune hypothyroidism or autoimmune Addison's disease, with values of 2.1, 2.2 and 2.2, respectively. For the group of patients without an autoimmune disorder, there was no significant difference (chi2 = 0.2; P = 0.64) in the frequency of the 106-bp allele when compared with control subjects. These results indicate that there is no association between the 106-bp allele and vitiligo, at least when the disorder occurs in the absence of an autoimmune disease.

Abatacept↗
PubMed1999

The psychological and emotional impact of acne and the effect of treatment with isotretinoin.

Although knowledge concerning the dermatological treatment of chronic acne has grown considerably in recent years, relatively few studies have assessed the impact of effective physical intervention upon the psychoemotional functioning of patients. Hypotheses regarding the psychological impact of acne were developed using concepts drawn from evolutionary psychology. A sample of 34 patients (19 men and 15 women) with chronic acne were assessed for psychological, emotional and dermatological symptomatology using a variety of self-report questionnaires over four time-points during 16 weeks treatment with isotretinoin. Thirty-four patients completed the first assessment, 21 the second, 20 the third and 15 the fourth and final assessment. At the first assessment, prior to isotretinoin treatment, 15 patients (44%) reported clinically significant levels of anxiety, while six patients (18%) reported clinically significant depression. Women with acne were significantly more embarrassed than their male counterparts about their skin disease. Treatment with isotretinoin produced significant improvements across a wide variety of psychological functions, although the emotional status of patients appeared to be more resistant to change. Acne appears to be a condition which has the potential to damage, perhaps even in the long term, the emotional functioning of some patients.

Acne Vulgaris↗
PubMed1999

Identification of epitopes on tyrosinase which are recognized by autoantibodies from patients with vitiligo.

The identification of tyrosinase autoantibodies in some patients with vitiligo has previously been reported. In this study we have determined the B cell epitopes on tyrosinase which are recognized by these autoantibodies. Deletion derivatives of tyrosinase cDNA were constructed and then translated in vitro with the concomitant incorporation of [35S]methionine into the protein products. The 35S-labeled tyrosinase derivatives were subsequently used in radioimmunoassays to investigate the reactivity of sera from five vitiligo patients. The epitope regions identified were: three in a central region of tyrosinase (amino acids 240-255, 289-294, and 295-300) and two others towards the C-terminal end of the protein (amino acids 435-447 and 461-479). Computer analysis of the potential B cell epitopes on tyrosinase revealed that the epitope regions recognized by the vitiligo sera were located in areas predicted to be highly antigenic. In addition, the centrally located antigenic regions (amino acids 289-294 and 295-300) had amino acid sequence homology to both tyrosinase-related protein-1 and -2. Thus, the epitopes on tyrosinase recognized by vitiligo patient sera are heterogeneous and include a region with homology to two related proteins which may explain the cross-reactivity previously noted between these antigens.

Adult↗
PubMed1999

Suspected fragrance allergy requires extended patch testing to individual fragrance allergens.

This study has been performed to evaluate the efficacy of fragrance mix (FM) as a screen for fragrance allergy. Patients were included if they had had positive allergic reactions to FM, to 1 of the 8 ingredients of FM, to 1 of 14 other fragrance materials, or to their own perfume. 91 patients were studied. There were 65 women and 23 men (in 3, their sex was not recorded) allergic to FM on patch testing. The mean (+/-SD) age was 48.4+/-18.6 years. 22 patients gave a past history of atopic eczema. Dermatitis of the hands (31%) and face (26%) were the most common presenting complaints. 85 patients (93%) had a positive allergic patch test reaction to FM. 22 of the 40 tested to the extended fragrance series were positive to other perfumes as well, and of these, there were 14 reactions (in 9 patients) to allergens not in the FM. In addition, 6 patients were positive only to separately tested fragrance constituents and not to the FM. In conclusion, FM is an accurate screen for fragrance contact sensitivity. However, patch testing to an extended series is needed if there is clinical suspicion of perfume allergy, as otherwise about 7% of patients allergic to fragrances will be missed.

Adult↗
PubMed1998

Nickel as an occupational allergen. A survey of 368 nickel-sensitive subjects.

OBJECTIVE: To define the role of nickel as an occupational allergen. DESIGN: Survey using path-test results. SETTING: Contact dermatitis clinic in the university hospital of a large industrial British city. PATIENTS: Three hundred sixty-eight nickel-allergic patients seen during a 5-year period were assessed for the relevance of nickel contact in their workplace. Patients were divided into possible occupational nickel allergy and nonoccupational nickel allergy groups. RESULTS: Nickel was considered an occupational allergen or possible occupational allergen in 84 (22.8%) of 368 patients shown to be nickel sensitive on patch testing. The main workers in whom nickel was a common allergen were hairdressers, retail clerks, caterers, domestic cleaners, and metalworkers. Those for whom occupational exposure was possible had a significantly higher prevalence of hand dermatitis compared with the nonoccupational nickel allergy group. Nickel allergy seemed to function as a secondary occupational influence, often in conjunction with other factors, such as irritants. CONCLUSIONS: Although the overall importance of nickel as an occupational allergen cannot be easily assessed, there is evidence of its importance in some occupations, especially those involving wet work. The possibility that nickel is acting as an occupational allergen needs to be assessed on an individual basis, taking into account personal circumstances and environment, but particularly should be considered in patients with hand dermatitis.

Adolescent↗
PubMed1998

Hamartomatous congenital melanocytic nevi showing secondary anetoderma-like changes.

A 47-year-old man had multiple large congenital melanocytic nevi associated with striking atrophic changes. Biopsy specimens showed a prominent reduction and fragmentation of elastic fibers in the papillary dermis. The anetoderma-like changes may have been secondary to a past inflammatory process but more likely represent a hamartoma.

Connective Tissue Diseases↗
PubMed1998

The participation of proliferative keratinocytes in the preimmune response to sensitizing agents.

The aims of this study were to investigate whether keratinocytes are capable of playing a direct preimmune role in the pathophysiology of allergic contact dermatitis (ACD) and to examine to what extent the degree of differentiation might influence this. We measured the ability of sensitizing agents to up-regulate intercellular adhesion molecule 1 (ICAM-1) expression in cultured normal human keratinocytes (NHK) and in the transformed human keratinocyte HaCaT cell line. In proliferative HaCaT cells, following a 24 h exposure, nickel compounds, para-phenylenediamine (pPD) and 1-chloro-2,4-dinitrobenzene produced a concentration-dependent up-regulation of ICAM-1 expression without reducing cell viability, while K2Cr2O7 led to ICAM-1 up-regulation at cytotoxic concentrations, and CrCl3 was without effect. In NHK, NiSO4 and pPD induced ICAM-1 expression to a significantly greater extent in proliferative cells than in differentiated cells, where involucrin expression was measured to assess the differentiation state. NiSO4- or pPD-pretreatment of proliferative HaCaT cells enhanced T-cell binding, which was abolished by neutralizing antibodies to ICAM-1 or CD18. Our investigations concerning the involvement of oxidative stress in the induction of ICAM-1 expression in response to sensitizing agents were inconclusive. The oxidizing agents FeCl3 and H2O2 up-regulated ICAM-1 expression in HaCaT cells but there was no clear relationship between the ability of agents to induce ICAM-1 expression and their ability to alter the levels of reduced glutathione. Although pPD increased interleukin-1 alpha release from NHK, this cytokine was not capable of inducing ICAM-1 expression in NHK. Tumour necrosis factor-alpha, which does induce ICAM-1 expression in NHK, was not detected in response to pPD, arguing against an autocrine pathway of ICAM-1 induction in response to pPD. In summary, we report the direct interaction of sensitizing agents with keratinocytes leading to the generation of immune signals, particularly by proliferative keratinocytes, suggesting an active role for the proliferative keratinocyte in the pathophysiology of ACD.

Allergens↗
PubMed1998

alpha-Melanocyte stimulating hormone inhibits tumour necrosis factor-alpha stimulated intercellular adhesion molecule-1 expression in normal cutaneous human melanocytes and in melanoma cell lines.

alpha-Melanocyte stimulating hormone (alpha-MSH) was found significantly to reduce tumour necrosis factor-alpha (TNF-alpha) stimulated upregulation of intercellular adhesion molecule-1 (ICAM-1) in normal adult cutaneous melanocytes. The maximum inhibitory response to alpha-MSH was obtained at around 10(-10) mol/L alpha-MSH when cells were coincubated with alpha-MSH and TNF-alpha for 24 h. alpha-MSH had little or no effect on basal ICAM-1 expression in melanocytes and the effects of alpha-MSH could be mimicked with 3-isobutyl-1-methylxanthine (IBMX). Preliminary data in three human melanoma cell lines also showed alpha-MSH and forskolin to be effective in significantly reducing TNF-alpha stimulated ICAM-1 expression over 24 h. The extent of the inhibition varied from cell line to cell line and was greatest in those cells with the highest number of alpha-MSH receptors. These data suggest that alpha-MSH has the ability to oppose the action of the pro-inflammatory cytokine TNF-alpha on melanocytes and melanoma cells.

1-Methyl-3-isobutylxanthine↗
PubMed1998

Autoantibodies to tyrosinase-related protein-1 detected in the sera of vitiligo patients using a quantitative radiobinding assay.

In the present study, we describe the in vitro transcription-translation of human tyrosinase-related protein-1 (TRP-1) cDNA and subsequent use of the resulting 35S-labelled TRP-1 in a radioimmunoassay to analyse vitiligo sera for the presence of TRP-1 antibodies. Of 53 vitiligo sera examined in the assay, three (5.7%) were found to be positive for TRP-1 antibodies. In contrast, sera from 20 controls, 10 patients with Hashimoto's thyroiditis and 10 patients with Graves' disease were all negative for TRP-1 antibodies. Although glycosylation of the labelled protein was necessary for its immunoprecipitation by TRP-1-specific monoclonal antibody TA99, this post-translational processing did not affect the binding of any of the sera tested. All three patients positive for TRP-1 antibodies (aged 50-63 years) had had vitiligo of the symmetrical type for more than 1 year, and all of them also had an associated autoimmune disorder: Graves' disease in one and autoimmune hypothyroidism in two. In addition, antibodies to the melanogenic enzymes tyrosinase and tyrosinase-related protein-2 (TRP-2) were present in their serum. Absorption studies indicated that preincubation with COS-7 cell extract containing either expressed TRP-1, tyrosinase or TRP-2 absorbed out the immunoreactivity of the three sera positive in the radioimmunoassay (RIA) with [35S]TRP-1. The results indicate that autoantibodies to TRP-1 cross-react with tyrosinase and TRP-2, suggesting one or more common epitopes between the three proteins.

Adolescent↗
PubMed1998

Vitiligo melanocytes in long-term culture show normal constitutive and cytokine-induced expression of intercellular adhesion molecule-1 and major histocompatibility complex class I and class II molecules.

The aetiology of vitiligo remains unclear. An autoimmune involvement has been suggested and, in this study, we examine whether melanocytes cultured from unaffected regions of the skin of vitiligo patients are more susceptible to immune attack by investigating constitutive and cytokine-stimulated expression of intercellular adhesion molecule-1 (ICAM-1) (under three media variants) and major histocompatibility complex (MHC) class I and class II (under one medium). Both normal and vitiligo melanocytes had similarly low constitutive expression of ICAM-1 and MHC class II molecules, whereas > 95% of cells had high constitutive expression of MHC class I. Normal and vitiligo melanocytes showed similar and significant increases in the expression of all three immune-related molecules in response to the cytokine, interferon-gamma. The expression of ICAM-1 was also similarly increased by the cytokine, tumour necrosis factor-alpha in both cells. Additionally, it was noted that, once the melanocyte cultures were established under experimental conditions, the rate of proliferation of vitiligo melanocytes did not differ significantly from that of normal melanocytes. In conclusion, we suggest that vitiligo melanocytes, once in culture, do not have intrinsic differences from normal melanocytes with respect to the expression of immune-related molecules.

Adult↗
PubMed1998

Autoantibodies to human melanocyte-specific protein pmel17 in the sera of vitiligo patients: a sensitive and quantitative radioimmunoassay (RIA).

In the present study we describe the in vitro transcription-translation of human melanocyte-specific protein Pmel17 cDNA and subsequent use of the resulting 35S-labelled Pmel17 in an RIA to analyse vitiligo sera for the presence of Pmel17 antibodies. Of 53 vitiligo sera examined in the assay, three (5.9%) were found to be positive for Pmel17 antibodies. In contrast, sera from 20 healthy controls, 10 patients with Hashimoto's thyroiditis and 10 patients with Graves' disease (GD) were all negative for Pmel17 antibodies. All three patients positive for Pmel17 antibodies (aged 50-63 years) had had vitiligo of the symmetrical type for > 1 year and all of them also had an associated autoimmune disorder: GD in one and autoimmune hypothyroidism in two. In addition, all three patients had antibodies to the melanogenic enzymes tyrosinase, tyrosinase-related protein-1 (TRP-1) and tyrosinase-related protein-2 (TRP-2) in their serum. Absorption studies indicated that preincubation with COS-7 cell extract containing expressed Pmel17 absorbed out the immunoreactivity of the three sera positive in the RIA, confirming the anti-Pmel17 reactivity of the sera from these patients. In contrast, COS-7 cell extracts containing either expressed tyrosinase, TRP-1 or TRP-2 did not remove the anti-Pmel17 reactivity of the three sera in the RIA. This lack of cross-reactivity suggests that the humoral response to Pmel17 in these patients is specific and independent of the antibody reactivity to tyrosinase, TRP-1 and TRP-2.

Absorption↗